Over the next five years the NIGMS P41 Proteomics Research Center for Integrative Biology Technology Research and Development (TR&D) efforts will focus on the needs of the biomedical research community in the context of Driving Biomedical Projects (DBPs) and collaborative projects that challenge the Center's technical capabilities. The three tightly integrated TR&Ds emphasize approaches for broadly characterizing proteins that include analysis of specific functions and activities, post-translational modifications, and other proteoforms; instrumental developments that enable more sensitive, quantitative, and high throughput proteomic measurements, including analyses of very small samples; and development of computational capabilities that provide improved quantitative proteomics measurements and facilitate proteomics data interpretation and subsequent integration with other data types, as well as their dissemination. The Center's technology developments will be evaluated in the context of a geographically diverse set of DBPs selected on the basis of their scientific and biomedical relevance, as well as their capacity to benefit from the Center's capabilities. These projects are essential to the Center, providing both direction for the early stage TR&D activities and test-beds for the developing technologies. The scope of the new DBP applications include the areas of protein quantification in signal transduction pathways, lipid-binding protein receptors, proteomic analysis of single pancreatic islets in diabetes, neuroproteomics, microbiome impact on lung transplant stability, oncogene regulation by PTMs, characterization of the intestinal host-pathogen interactome, embryonic survival and implantation, and functional annotation of drug resistant Mtb strains. In addition to these DBPs will be a host of new collaborative and service projects that benefit from distinct Center capabilities. The Center will train researchers in the ue of the adva